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Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer

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ClinicalTrials.gov Identifier: NCT03307629
Recruitment Status : Recruiting
First Posted : October 12, 2017
Last Update Posted : December 5, 2018
Sponsor:
Information provided by (Responsible Party):
Noxopharm Limited

Brief Summary:
The study is intended as a Proof of Concept and dose confirmation study. The primary objective of this study is to observe safety and tolerability of idronoxil (NOX66) in combination with radiotherapy (at palliative doses) in patients with metastatic castrate-resistant prostate cancer (CRPC) and to confirm dose in order to progress to Phase 2/3.

Condition or disease Intervention/treatment Phase
Cancer Drug: NOX66 Radiation: Irradiation Therapy Phase 1

Detailed Description:

This study will investigate three escalating doses of NOX66 in combination with palliative dose of radiation therapy to establish safety profile and / or obtain efficacy signals and to determine the optimal dose for future radiation therapy combination studies.

The key hypotheses to be tested in this study are:

  1. That NOX66 can be safely added to palliative dose radiation therapy.
  2. That NOX66 may sensitise tumours to palliative doses of radiation therapy
  3. That NOX66 in combination with radiation therapy may trigger or augment an abscopal effect

Participants will have a minimum of 1 symptomatic lesion amenable to radiation therapy.

Radiation therapy will be delivered at a 20Gy dosage over 5 fractions. NOX66 will be taken on 13 consecutive days starting 1 day prior to radiotherapy.

The response of irradiated and non-irradiated target tumour lesions will be measured by CT/MRI scan and RECIST1.1 criteria at three time points post treatment. Pain response will be evaluated using the Brief Pain Inventory-Short Form (BPI-SF) instrument at five time points post treatment.

Patients will be suitable for the study as they become indicated for palliative radiation therapy for management of their cancer.

This study will enrol up to 24 patients in 3 NOX66 dose level cohorts of 4 patients (n=12) and an expansion cohort of 12 patients. Dose escalation decisions will be based on patients who experience adverse events directly related to NOX66 treatment.

Following the review of accumulated safety data, disease status and treatment efficacy signals at WEEK 6 for the first 12 patients, the Study Steering Committee will determine the dose at which to continue treatment for the expansion patient Cohort 4 in the study. A further 12 patients will be recruited at this dose level.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: NOX66 and Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer - a Phase 1b Proof of Concept and Dose Confirmation Study
Actual Study Start Date : November 1, 2017
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : December 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: NOX66 + Radiation treatment (combined) in cohorts 1-3

NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle.

NOX66 treatment given to 3 cohorts of 4 patients as 1 of 3 doses, 400mg, 800mg and 1200 mg.

Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.

Drug: NOX66
NOX66 delivered as rectal suppository.

Radiation: Irradiation Therapy
Radiation per selected tumour lesion.

Experimental: NOX66 + Radiation treatment (combined) in cohort 4

NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle.

NOX66 dose will be either one of 3 doses 400mg, 800mg and 1200 mg based on interim analyses of safety data and tumour response at WEEK 6 of 3 dose cohorts of 12 total patients. The SSC will inform on dose for cohort expansion.

Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.

Drug: NOX66
NOX66 delivered as rectal suppository.

Radiation: Irradiation Therapy
Radiation per selected tumour lesion.




Primary Outcome Measures :
  1. Change of incidence of Treatment-Emergent Adverse Events including SAEs [Safety and Tolerability] of NOX66 combined with radiation therapy between multiple timepoints [ Time Frame: Day 2, Day 6, EOT and from enrolment up to week 6, week 12, week 24 ]
    Safety will be assessed through reported incidence of treatment emergent adverse events (AEs), including SAEs, dose limiting toxicities, AEs leading to withdrawal, events of at least CTCAE Version 4.03 Grade 2 in severity. Treatment emergent AEs are those with an onset on or after the initiation of therapy. Timepoints for AE /SAE assessment are Day 2 (start of radiation therapy treatment and one day after start of NOX66 treatment), Day 6, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.

  2. Assessment of laboratory results [ Time Frame: Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24. ]
    Other safety endpoints include laboratory results which are assessed at Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.

  3. Assessment of ECG results [ Time Frame: Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24. ]
    Further safety endpoints include laboratory results and ECG findings which are assessed Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.


Secondary Outcome Measures :
  1. Change of tumour size in patients according to RECIST 1.1 criteria [ Time Frame: From enrolment up to week 6, week 12, week 24 ]
    Change from baseline in RECIST 1.1 criteria of tumour size of target irradiated and non-irradiated lesions on radiologic scans, as assessed by the investigator based on CT/MRI scan. RECIST 1.1 criteria are Complete Response (CR), Partial Response (PR), Stable Disease(SD) and Progressive Disease (PD)

  2. Change and measurement of non-target lesions according to RECIST [ Time Frame: From enrolment up to week 6, week 12, week 24 ]
    Observation of change from baseline in Non-target lesions according to RECIST 1.1 criteria

  3. Change in overall pain score assessment by using BPI-SF [ Time Frame: From enrolment up to week 6, week 12, week 18, week 24 ]
    Change from baseline in pain score based on responses to BPI-SF

  4. Increase or decrease of PSA levels [ Time Frame: From enrolment up to week 6, week 12, week 24 ]
    Change from baseline in PSA levels

  5. Change of ECOG value [ Time Frame: From enrolment up to week 6, week 12, week 24 ]
    Assessment of patient via ECOG status

  6. Assessment of change in physical appearance (physical exam) by measuring HEENT, gastrointestinal, abdominal status on multiple timepoints [ Time Frame: From enrolment up to Day 2, End of Treatment (day 16-17), week 6, week 12, week 24 ]
    Assessment of patient via physical exam.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of informed consent
  2. ≥ 18 years of age
  3. Histologically confirmed prostate cancer and/or PSA of >100 ng/mL at original diagnosis
  4. Metastatic disease evidenced by either CT/MRI imaging or bone scan
  5. Objective evidence of disease progression as defined by either:

    i. Radiographic progression of in nodal or visceral metastases and bone disease progression with 2 or more new lesions ii. Rising PSA value ≥2ng/ml in at least 3 measurements, at least 1 week apart, with castrate levels of serum testosterone.

  6. Eligible to receive palliative radiation therapy for management of disease
  7. At least one symptomatic lesion which is suitable for radiation therapy
  8. ECOG Performance status 0-2
  9. A minimum life expectancy of 24 weeks
  10. Adequate bone marrow, hepatic and renal function as evidenced by:

    • Absolute neutrophil count (ANC) > 1.5 x 109/L
    • Platelet count > 100 x 109/L
    • Hemoglobin > 9.0 g/dL
    • Serum bilirubin < 1.5 x ULN
    • AST/ALT (SGOT/SGPT) < 2.5 x ULN for the reference laboratory or < 5 x ULN in the presence of liver metastases
    • Serum creatinine < 1.5 x ULN
  11. Ongoing androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist
  12. At least 4 weeks must have elapsed prior to commencement of NOX66 treatment since prior chemotherapy, investigational drug or biologic therapy and any toxicity associated with these treatments has recovered to ≤ NCI-CTCAE (version 4.03) Grade 1.
  13. At least 21 days must have elapsed following major surgery and any surgical incision should be completely healed.

Exclusion Criteria:

  1. Tumour involvement of the central nervous system
  2. Uncontrolled infection or systemic disease
  3. Clinically significant cardiac disease not well controlled with medication (e.g. congestive heart failure, symptomatic coronary artery disease, angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months

    • Patients with a QTc > 470 msec on screening ECG

  4. Concurrent systemic chemotherapy or biological therapy
  5. Any situation where the use of suppository therapy is contra-indicated or impractical (eg. chronic diarrhoea, colostomy, ulcerative colitis).
  6. Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both)
  7. Any subject whose testosterone is not suppressed i.e. is > 0.5nmols/L
  8. Any other reason which, in the opinion of the investigator, will preclude suitable participation in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03307629


Contacts
Contact: Anne Capp, FRANZCR (+61) 2 49184500 Anne.Capp@cancer.com.au

Locations
Australia, New South Wales
Genesis Cancer Care - Newcastle Recruiting
Newcastle, New South Wales, Australia, 2290
Contact: Anne Capp    (+61) 2 4918 4500    anne.capp@cancer.com.au   
Central West Cancer Care Centre - Orange Health Service Recruiting
Orange, New South Wales, Australia, 2800
Contact: Catherine Richards    (02) 6369 3380    Catherine.richards2@health.nsw.gov.au   
Principal Investigator: Rob Zielinski, Dr         
Genesis Cancer Care Mater Hospital Recruiting
Sydney, New South Wales, Australia, 2060
Contact: Bianca Karle    (02) 9458 8050    bianca.karle@cancer.com.au   
Principal Investigator: Michael Izard, AProf         
North West Cancer Centre, Tamworth Hospital Recruiting
Tamworth, New South Wales, Australia, 2340
Contact: Margaret Chamen    (02) 6767 7760    margaret.chamen@hnehealth.nsw.gov.au   
Principal Investigator: Carolin Round, Dr         
Australia, Queensland
Radiation Oncology Centres Gold Coast Recruiting
Gold Coast, Queensland, Australia, 4215
Contact: Dainelle Miller    (07) 5687 2351    millerd@roc.team   
Principal Investigator: Jim Jackson, DR         
New Zealand
Canterbury Urology Research Trust Recruiting
Christchurch, New Zealand, 8013
Contact: Barbara Gordon    + 64 (0)3 355 2426    barbara@medicaltrials.co.nz   
Contact: Liz Mitchell    + 64 (0)3 355 2426    liz@medicaltrials.co.nz   
Principal Investigator: Chris Wynne, Dr         
Sponsors and Collaborators
Noxopharm Limited
Investigators
Study Chair: Marinella Messina, PhD Noxopharm Limited

Responsible Party: Noxopharm Limited
ClinicalTrials.gov Identifier: NCT03307629     History of Changes
Other Study ID Numbers: NOX66-002A
First Posted: October 12, 2017    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data for primary and secondary outcome measure will be made available within 12 months after study completion.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: 12 months after study completion

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases